ArticlePsychopharmacology2013
Effects of the adenosine A2A antagonist istradefylline on cognitive performance in rats with a 6-OHDA lesion in prefrontal cortex.
Article in Psychopharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- Quantifying the inverted U: A meta-analysis of prefrontal dopamine, D1 receptors, and working memory.Behavioral neuroscience · 2022Pooled it
- Neurotransmitter Systems in Alzheimer's Disease.Current issues in molecular biology · 2026Review
- The Anti-Parkinsonian A2A Receptor Antagonist Istradefylline (KW-6002) Attenuates Behavioral Abnormalities, Neuroinflammation, and Neurodegeneration in Cerebral Ischemia: An Adenosinergic Signaling Link Between Stroke and Parkinson's Disease.International journal of molecular sciences · 2025Article
- Adolescent alcohol exposure disrupts episodic-like memory by impairing dopamine synapses in the mouse prelimbic cortex.Neuropharmacology · 2025Article
- Impact of istradefylline on motor and non-motor symptoms in patients with Parkinson's disease: Subanalysis of the ISTRA ADJUST PD.Clinical parkinsonism & related disorders · 2025Article
- Targeting the adenosine AChinese journal of traumatology = Zhonghua chuang shang za zhi · 2024Review
- Trends on Novel Targets and Nanotechnology-Based Drug Delivery System in the Treatment of Parkinson's disease: Recent Advancement in Drug Development.Current drug targets · 2024Review
- Striatopallidal adenosine ANeuropharmacology · 2023Review
- Promising biomarkers and therapeutic targets for the management of Parkinson's disease: recent advancements and contemporary research.Metabolic brain disease · 2023Review
- Therapeutic Approaches to Non-Motor Symptoms of Parkinson's Disease: A Current Update on Preclinical Evidence.Current neuropharmacology · 2023Article
- The Pharmacological Potential of Adenosine AMolecules (Basel, Switzerland) · 2022Review
- Emerging Nondopaminergic Medications for Parkinson's Disease: Focusing on A2A Receptor Antagonists and GLP1 Receptor Agonists.Journal of movement disorders · 2021Article
- Combined Therapy of AMolecules (Basel, Switzerland) · 2021Article
- Experimental Models of Cognitive Impairment for Use in Parkinson's Disease Research: The Distance Between Reality and Ideal.Frontiers in aging neuroscience · 2021Review
- The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties.Neuroscience and biobehavioral reviews · 2020Review
- Shared cerebral metabolic pathology in non-transgenic animal models of Alzheimer's and Parkinson's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2020Review
- Impact of Coffee and Cacao Purine Metabolites on Neuroplasticity and Neurodegenerative Disease.Neurochemical research · 2019Review
- Adenosine ABritish journal of pharmacology · 2018Article
- Adenosine AFrontiers in pharmacology · 2018Article
- The Impact of Purinergic System Enzymes on Noncommunicable, Neurological, and Degenerative Diseases.Journal of immunology research · 2018Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleAltered cognitive function is a common feature of both the early and later stages of Parkinson's disease (PD) that involves alterations in cortical dopamine content. Adenosine A2A antagonists, such as istradefylline, improve motor function in PD, but their effect on cognitive impairment has not been determined.
objectiveThe present study investigated whether impairment of working memory due to the loss of dopaminergic input into the prefrontal cortex (PFC) is reversed by administration of istradefylline. We also evaluated whether A2A antagonist administration modulates dopamine levels in the PFC.
methodsBilateral lesions of the dopaminergic input to the PFC were produced in rats using 6-hydroxydopamine (6-OHDA). Cognitive performance was evaluated using an object recognition task and delayed alternation task. The effects of istradefylline, donepezil and methamphetamine on cognitive performance were examined. In addition, the effect of istradefylline on extracellular dopamine levels in the PFC was studied.
resultsPFC dopamine levels and cognitive performance were significantly reduced by 6-OHDA lesioning. Istradefylline, donepezil and methamphetamine improved cognitive performance of PFC-lesioned rats. Istradefylline increased dopamine levels in the PFC in both normal and PFC-lesioned rats.
conclusionsPFC dopaminergic input plays an important role in working memory performance. Blockade of A2A receptors using istradefylline reverses the changes in cognitive function, and this may be due to an increase in PFC dopamine content. Adenosine A2A receptor antagonists not only improve motor performance in PD but may also lead to improved cognition.
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